Background: Transcranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in ... [more ▼]

Background: Transcranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in patients in vegetative state (VS) (now known as unresponsive wakefulness syndrome, UWS) and minimally conscious (MCS) states due to severe brain damage remains largely unknown. Objective/hypothesis: It was hypothesized that cortical motor excitability would be decreased and would correlate to the level of consciousness in patients with disorders of consciousness. Methods: Corticospinal excitability was assessed in 47 patients (24 VS/UWS and 23 MCS) and 14 healthy controls. The test parameters included maximal peak-to-peak M-wave (Mmax), F-wave persistence, peripheral and central motor conduction times, sensory (SEP) and motor evoked (MEP) potential latencies and amplitudes, resting motor threshold (RMT), stimulus/response curves, and short latency afferent inhibition (SAI). TMS measurements were correlated to the level of consciousness (assessed using the Coma Recovery Scale-Revised). Results: On average, the patient group had lower Mmax, lower MEP and SEP amplitudes, higher RMTs, narrower stimulus/response curves, and reduced SAI compared to the healthy controls (P < 0.05). The SAI alterations were correlated to the level of consciousness (P < 0.05). Conclusions: The findings demonstrated the impairment of the cortical inhibitory circuits in patients with disorders of consciousness. Moreover, the significant relationship was found between cortical inhibition and clinical consciousness dysfunction. [less ▲]

Background: Familial hemiplegic migraine (FHM) is a rare, dominantly inherited subtype of migraine with transient hemiplegia during the aura phase. Mutations in at least three different genes can produce ... [more ▼]

Background: Familial hemiplegic migraine (FHM) is a rare, dominantly inherited subtype of migraine with transient hemiplegia during the aura phase. Mutations in at least three different genes can produce the FHM phenotype. The mutated FHM genes code for ion transport proteins that animal and cellular studies have associated with disturbed ion homeostasis, altered cellular excitability, neurotransmitter release, and decreased threshold for cortical spreading depression. The common forms of migraine are characterized interictally by a habituation deficit of cortical and subcortical evoked responses that has been attributed to neuronal dysexcitability. FHM and the common forms of migraine are thought to belong to a spectrum of migraine phenotypes with similar pathophysiology, and we therefore examined whether an abnormal habituation pattern would also be found in FHM patients. Methods: In a group of genotyped FHM patients (five FHM-1, four FHM-2), we measured habituation of visual evoked potentials (VEP), auditory evoked potentials including intensity dependence (IDAP), the nociception-specific blink reflex (nsBR) and compared the results to a group of healthy volunteers (HV). Results: FHM patients had a more pronounced habituation during VEP (P = 0.025) and nsBR recordings (P = 0.023) than HV. There was no difference for IDAP, but the slope tended to be steeper in FHM. Conclusion: Contrary to the common forms of migraine, FHM patients are not characterized by a deficient, but rather by an increased habituation in cortical/brain stem evoked activities. These results suggest differences between FHM and the common forms of migraine, as far as central neuronal processing is concerned. [less ▲]

Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4-6 h after administration. The causative mechanisms are not known, but the long delay leaves room for a central ... [more ▼]

Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4-6 h after administration. The causative mechanisms are not known, but the long delay leaves room for a central effect, such as a change in neuronal excitability and synaptic transmission of various CNS areas involved in pain and behaviour including trigeminal nucleus caudalis and monoaminergic brain stem nuclei. To explore the central action of NTG, we have studied its effects on amplitude and habituation of the nociceptive blink reflex (nBR) and the visual evoked potential (VEP) before, 1 h and 4 h after administration of NTG (1.2 mg sublingual) or placebo (vehicle sublingual) in two groups of 10 healthy volunteers. We found a significant decrease in nBR pain and reflex thresholds both 1 and 4 h post-NTG. At the 4 h time point R2 latency was shorter (p=0.04) and R2 response area increased (p<0.01) after NTG but not after placebo. Habituation tended to become more pronounced after both NTG and placebo administration. There was a significant amplitude increase in the 5th VEP block (p=0.03) at 1h after NTG and in the 1st block (p=0.04) at 4 h. VEP habituation was replaced by potentiation at both delays after NTG; the change in habituation slope was significant at 1h (p=0.02). There were no significant VEP changes in subjects who received sublingual placebo. In conclusion, we found that in healthy subjects sublingual NTG, but not its vehicle, induces changes in a trigeminal nociceptive reflex and an evoked cortical response which are comparable to those found immediately before and during an attack of migraine. These changes could be relevant for the attack-triggering effect of NTG in migraineurs. [less ▲]

in Cephalalgia : An International Journal of Headache (2008), 28(9), 988-90

The amplitude and habituation of the click-evoked vestibulo-collic reflex (VCR) was found reduced between attacks in migraineurs without complaints of ictal or interictal vertigo or dizziness, compared ... [more ▼]

The amplitude and habituation of the click-evoked vestibulo-collic reflex (VCR) was found reduced between attacks in migraineurs without complaints of ictal or interictal vertigo or dizziness, compared with healthy subjects. As a next step we recorded VCR in 17 migraine patients (eight with migraine without aura and nine with migraine with aura) who presented ictal migrainous vertigo according to the criteria defined by Neuhauser et al., using a method described previously. Migraineurs with migrainous vertigo have similar VCR abnormalities as patients without vertigo, i.e. a decreased global amplitude and absence of habituation. Potentiation seemed more pronounced in migraineurs with vertigo (7.46 +/- 18.6), but the difference was not significant. [less ▲]

In previous studies, we described subclinical abnormalities of neuromuscular transmission and cerebellar functions in migraineurs. The aim of this study was to search if these two functions are correlated ... [more ▼]

In previous studies, we described subclinical abnormalities of neuromuscular transmission and cerebellar functions in migraineurs. The aim of this study was to search if these two functions are correlated in the same patient. Thirteen migraineurs [five without aura (MO) and eight with aura (MA)] underwent both stimulation-SFEMG and 3D-movement analysis. Single fiber EMG (SFEMG) results were expressed as the "mean value of consecutive differences" (mean MCD). Precision of arm-reaching movements (measured with an infrared optoelectronic tracking system) was expressed as the average deviation in the horizontal plane. Median values of mean MCD and mean horizontal deviation were not different between MO and MA. However, in MA, but not in MO, both variables were positively correlated. Thus, we conclude that neuromuscular transmission and cerebellar functions are correlated in the same patient when affected by migraine with aura. We suggest that this correlation might be due to a common molecular abnormality. [less ▲]

in Cephalalgia : An International Journal of Headache (2007), 27(10), 1150-1155

Interictal evoked central nervous system responses are characterized in migraineurs by a deficit of habituation, at both cortical and subcortical levels. The click-evoked vestibulo-collic reflex (VCR ... [more ▼]

Interictal evoked central nervous system responses are characterized in migraineurs by a deficit of habituation, at both cortical and subcortical levels. The click-evoked vestibulo-collic reflex (VCR) allows the assessment of otolith function and an oligosynaptic pathway linking receptors in the saccular macula to motoneurons of neck muscles. Three blocks of 75 averaged responses to monaural 95-dB normal hearing level 3-Hz clicks were recorded over the contracted ipsilateral sternocleidomastoid muscle in 25 migraineurs between attacks and 20 healthy subjects, without vestibular symptoms. Amplitudes, raw and corrected for baseline electromyography, were significantly smaller in migraine patients. Whereas in healthy volunteers the VCR habituated during stimulus repetition (-4.96% +/- 14.3), potentiation was found in migraineurs (4.34% +/- 15.3; P = 0.04). The combination with a reduced mean amplitude does not favour vestibular hyperexcitability as an explanation for the habituation deficit in migraine, but rather an abnormal processing of repeated stimuli in the reflex circuit. [less ▲]

Coppola G, Di Clemente L, Fumal A, Magis D, De Pasqua V, Pierelli F & Schoenen J. Inhibition of the nociceptive R2 blink reflex after supraorbital or index finger stimulation is normal in migraine without aura between attacks. Cephalalgia 2007; 27:803-808. London. ISSN 0333-1024 In order to explore possible interictal brainstem dysfunctions in migraine, we have studied the R2 component of the nociceptive specific blink reflex (nBR) after conditioning by supraorbital or index finger stimuli in 14 untreated migraine without aura patients (MO) between attacks and in 15 healthy volunteers. We determined the R2 recovery curve at increasing inter-stimulus intervals between 50 and 600 ms. The nBR was conditioned by a paired supraorbital stimulus and, in another session, by an ipsilateral electrical shock delivered to the index finger. The R2 nBR recovery curves were normal in MO patients for both the supraorbital and peripheral conditioning. These results do not favour persistent interictal sensitization in the spinal trigeminal sensory system. They also suggest that the control exerted by descending brainstem pathways on medullary R2 interneurones is normal in migraine between attacks. [less ▲]

Background Drug-resistant chronic duster headache (drCCH) is a devastating disorder for which various destructive procedures have been tried unsuccessfully. Occipital nerve stimulation (ONS) is a new ... [more ▼]

Background Drug-resistant chronic duster headache (drCCH) is a devastating disorder for which various destructive procedures have been tried unsuccessfully. Occipital nerve stimulation (ONS) is a new, safe strategy for intractable headaches. We undertook a prospective pilot trial of ONS in drCCH to assess clinical efficacy and pain perception. Methods Eight patients with drCCH had a suboccipital neurostimulator implanted on the side of the headache and were asked to record details of frequency, intensity, and symptomatic treatment for their attacks in a diary before and after Continuous ONS. To detect changes in cephalic and extracephalic pain processing we measured electrical and pressure pain thresholds and the nociceptive blink reflex. Findings Two patients were pain free after a follow-up of 16 and 22 months; one of them still had occasional autonomic attacks. Three patients had around a 90% reduction in attack frequency. Two patients, one of whom had had the implant for only 3 months, had improvement of around 40%. Mean follow-up was 15.1 months (SD 9.5, range 3-22). Intensity of attacks tends to decrease earlier than frequency during ONS and, on average, is improved by 50% in remaining attacks. All but one patient were able to substantially reduce their preventive drug treatment. Interruption of ONS by switching off the stimulator or because of an empty battery was followed within days by recurrence and increase of attacks in all improved patients. ONS did not significantly modify pain thresholds. The amplitude of the nociceptive blink reflex increased with longer durations of ONS. There were no serious adverse events. Interpretation ONS could be an efficient treatment for drCCH and could be safer than deep hypothalamic stimulation. The delay of 2 months or more between implantation and significant clinical improvement suggests that the procedure ads via slow neuromodulatory processes at the level of upper brain stem or diencephalic centres. [less ▲]

Habituation of the nociception-specific blink reflex (nBR) is reduced interictally in migraine patients. This could be related to the habituation deficit of evoked cortical responses, a reproducible ... [more ▼]

Habituation of the nociception-specific blink reflex (nBR) is reduced interictally in migraine patients. This could be related to the habituation deficit of evoked cortical responses, a reproducible abnormality in migraine which has a familial character, or to central trigeminal sensitization due to repeated attacks. We compared nBR habituation in healthy volunteers devoid of personal or family history of migraine (HV), in migraine without aura patients (MO) and in healthy volunteers with a family history of migraine in first degree relatives (HV-F). We elicited the nBR by stimulating the right supraorbital region with a custom-built electrode in 16 MO between attacks, 15 HV and 14 HV-F. Habituation was measured as the percentage area-under-the-curve decrease in 10 consecutive blocks of five averaged rectified responses. nBR habituation was clearly reduced in MO and HV-F compared to HV. Percentage area under the curve decreased between the 1st and the 10th block by 55.01% in HV, 25.71% in MO (P = 0.001) and 26.73% in HV-F (P = 0.043). HV-F had the most pronounced abnormality with potentiation instead of habituation in the second block. We found a positive intraindividual correlation between attack frequency and habituation in MO (r = 0.621; P = 0.010). Migraine patients have interictally a deficient habituation of the nBR which is inversely related to attack frequency, suggesting that it is not due to trigeminal sensitization. Surprisingly, the most pronounced habituation deficit is found in asymptomatic individuals with a family history of migraine. Deficient nBR habituation could thus be a trait marker for the genetic predisposition to migraine. [less ▲]

We enrolled six patients suffering from refractory chronic cluster headache in a pilot trial of neurostimulation of the ipsilateral ventroposterior hypothalamus using the stereotactic coordinates ... [more ▼]

We enrolled six patients suffering from refractory chronic cluster headache in a pilot trial of neurostimulation of the ipsilateral ventroposterior hypothalamus using the stereotactic coordinates published previously. After the varying durations needed to determine optimal stimulation parameters and a mean follow-up of 14.5 months, the clinical outcome is excellent in three patients (two are pain-free; one has fewer than three attacks per month), but unsatisfactory in one patient, who only has had transient remissions. Mean voltage is 3.28 V, diplopia being the major factor limiting its increase. When the stimulator was switched off in one pain-free patient, attacks resumed after 3 months until it was turned on again. In one patient the implantation procedure had to be interrupted because of a panic attack with autonomic disturbances. Another patient died from an intracerebral haemorrhage that developed along the lead tract several hours after surgery; there were no other vascular changes on post-mortem examination. After 1 month, the hypothalamic stimulation induced resistance against the attack-triggering agent nitroglycerin and tended to increase pain thresholds at extracephalic, but not at cephalic, sites. It had no detectable effect on neurohypophyseal hormones or melatonin excretion. We conclude that hypothalamic stimulation has remarkable efficacy in most, but not all, patients with treatment-resistant chronic cluster headache. Its efficacy is not due to a simple analgesic effect or to hormonal changes. Intracerebral haemorrhage cannot be neglected in the risk evaluation of the procedure. Whether it might be more prevalent than in deep-brain stimulation for movement disorders remains to be determined. [less ▲]

A deficit of habituation in cortical information processing, including somatosensory evoked potentials (SSEPs), is the most consistent neurophysiological abnormality in migraine patients between attacks ... [more ▼]

A deficit of habituation in cortical information processing, including somatosensory evoked potentials (SSEPs), is the most consistent neurophysiological abnormality in migraine patients between attacks. To explore further the mechanisms underlying this interictal neural dysfunction, we have studied the high-frequency oscillations (HFOs) embedded in SSEPs because they are thought to reflect spike activity in thalamo-cortical cholinergic fibres (early HFOs) and in cortical inhibitory GABAergic interneurons (late HFOs). Untreated migraine patients with (MA) and without (MO) aura were recorded during (n = 13: nine MO, four MA) and between attacks (n = 29: 14 MO, 15 MA) and compared with healthy volunteers. SSEPs were filtered off-line (digital band-pass between 450 and 750 Hz) to extract the two HFO bursts from the broad-band contralateral N20 somatosensory cortical response obtained by median nerve stimulation. In both migraine groups, amplitudes and latencies of conventional broad-band SSEPs recorded interictally from cervical and parietal active electrodes were not significantly different from those found in healthy volunteers. In contrast, maximum peak-to-peak amplitude and area under the rectified curve of the early HFO burst were significantly smaller in both MA and MO patients than in healthy volunteers. There was no significant difference in the later HFO burst between migraineurs and healthy volunteers. During attacks, all electrophysiological measurements in migraineurs were similar to those found in healthy volunteers. Thalamo-cortical activation, as reflected by the early SSEP HFO burst, may thus be reduced in migraine interictally, but normalizes during an attack, whereas intracortical inhibition, as indexed by the late HFO burst, is normal at any time. This supports the hypothesis that the habituation deficit in migraineurs is due to a reduced pre-activation level of sensory cortices and not to increased cortical excitability or reduced intracortical inhibition. [less ▲]